A biochemical study of the antidiabetic and anticogulant effects of Tulbaghia Violacea

Secondary metabolites derived from plants, especially those used by traditional healers, are at the forefront of new drug development in combating diseases such as cancer and diabetes. Garlic is employed in indigenous medicine all over the world for the treatment of a variety of diseases. Dietary garlic has been recognized for its beneficial health effects. In particular, garlic consumption has been correlated with (i) reduction of risk factors for cardiovascular diseases and cancer, (ii) stimulation of immune function, (iii) enhanced detoxification of foreign compounds, (iv) hepatoprotection, (v) antimicrobial effects, (vi) antioxidant effects, and most importantly (vii) its hypoglycemic and anticoagulant properties. Due to these beneficial properties, garlic and its closely related genera which includes Tulbaghia violacea, may be useful as coadjuvant therapy in the treatment of type 2 diabetes and some of its physiological complications. The aim of this study was to determine if T. violacea has antidiabetic and anticoagulant properties. This was performed in vitro using both aqueous and organic extracts of the roots, leaves and bulbs. An organic extract was able to improve glucose-stimulated insulin secretion (GSIS) in INS-1 pancreatic β-cells and glucose uptake in Chang liver cells. The BO extract had no effect on the glucose uptake in 3T3-L1 an adipose cell line and reduced glucose utilisation in C2C12, a skeletal muscle cell line. Some of the properties displayed by T. violacea in this study are consistent with those found in similar studies with garlic extracts. It was observed that the BO extract increased the membrane potential and Glut-2 expression in INS-1 cells cultured at hyperglycemic levels, however, at normoglycemic levels a reduction was observed. The oxygen consumption increased at both glycemic levels due to treatment with the BO extract. Platelets were exposed to the extracts to determine their effects upon platelet aggregation, adhesion and protein secretion. Since the BO extract displayed the highest potential at inhibiting platelet aggregation and adhesion. A rat model was used in ex vivo studies to determine if the extract exhibited the same effect in a physiological model. It was noted that the BO extract exhibited a higher degree of inhibition on platelet aggregation and adhesion than the positive control, aspirin. The BO extract reduced clotting times in the prothrombin time (PT) test, but prolonged the clotting time in the actived partial thromboplastin time (APTT) assay in the ex vivo model; however, it had no affect on these clotting assays in the in vitro model using human blood. The BO extract increased the D-dimer and Fibrinogen-C levels in the in vitro model, but had no effect on the D-dimer concentrations and lowered the Fibrinogen-C levels in the ex vivo model. The active compounds in the extract remain to be elucidated

Using Whole Genome Sequencing to Characterize Clinically Significant Blood Groups Among Healthy Older Australians

There have been no comprehensive studies of a full range of blood group polymorphisms within the Australian population. This problem is compounded by the absence of any databases carrying genomic information on chronically transfused patients and low frequency blood group antigens in Australia. Here, we use RBCeq, a web server-based blood group genotyping software, to identify unique blood group variants among Australians and compare the variation detected vs global data. Whole-genome sequencing data were analyzed for 2796 healthy older Australians from the Medical Genome Reference Bank and compared with data from 1000 Genomes phase 3 (1KGP3) databases comprising 661 African, 347 American, 503 European, 504 East Asian, and 489 South Asian participants. There were 661 rare variants detected in this Australian sample population, including 9 variants that had clinical associations. Notably, we identified 80 variants that were computationally predicted to be novel and deleterious. No clinically significant rare or novel variants were found associated with the genetically complex ABO blood group system. For the Rh blood group system, 2 novel and 15 rare variants were found. Our detailed blood group profiling results provide a starting point for the creation of an Australian blood group variant database.</p

RBCeq: A robust and scalable algorithm for accurate genetic blood typing

Background: While blood transfusion is an essential cornerstone of hematological care, patients requiring repetitive transfusion remain at persistent risk of alloimmunization due to the diversity of human blood group polymorphisms. Despite the promise, user friendly methods to accurately identify blood types from next-generation sequencing data are currently lacking. To address this unmet need, we have developed RBCeq, a novel genetic blood typing algorithm to accurately identify 36 blood group systems. Methods: RBCeq can predict complex blood groups such as RH, and ABO that require identification of small indels and copy number variants. RBCeq also reports clinically significant, rare, and novel variants with potential clinical relevance that may lead to the identification of novel blood group alleles. Findings: The RBCeq algorithm demonstrated 99·07% concordance when validated on 402 samples which included 29 antigens with serology and 9 antigens with SNP-array validation in 14 blood group systems and 59 antigens validation on manual predicted phenotype from variant call files. We have also developed a user-friendly web server that generates detailed blood typing reports with advanced visualization (https://www.rbceq.org/). Interpretation: RBCeq will assist blood banks and immunohematology laboratories by overcoming existing methodological limitations like scalability, reproducibility, and accuracy when genotyping and phenotyping in multi-ethnic populations. This Amazon Web Services (AWS) cloud based platform has the potential to reduce pre-transfusion testing time and to increase sample processing throughput, ultimately improving quality of patient care. Funding: This work was supported in part by Advance Queensland Research Fellowship, MRFF Genomics Health Futures Mission (76,757), and the Australian Red Cross LifeBlood. The Australian governments fund the Australian Red Cross Lifeblood for the provision of blood, blood products and services to the Australian community.</p